Abstract
The urothelium is a specialized epithelium that lines the urinary tract. It consists of three different cell types, namely, basal, intermediate and superficial cells arranged in relatively distinct cell layers. Normally, quiescent, it regenerates fast upon injury, but the regeneration process is not fully understood. Although several reports have indicated the existence of progenitors, their identity and exact topology, as well as their role in key processes such as tissue regeneration and carcinogenesis have not been clarified. Here we show that a minor subpopulation of basal cells, characterized by the expression of keratin 14, possesses self-renewal capacity and also gives rise to all cell types of the urothelium during natural and injury-induced regeneration. Moreover, these cells represent cells of origin of urothelial cancer. Our findings support the hypothesis of basally located progenitors with profound roles in urothelial homoeostasis.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Biomarkers, Tumor / genetics*
-
Biomarkers, Tumor / metabolism
-
Cell Differentiation
-
Cell Lineage / drug effects
-
Cell Lineage / genetics
-
Cell Proliferation
-
Cell Transformation, Neoplastic / genetics*
-
Cell Transformation, Neoplastic / metabolism
-
Cell Transformation, Neoplastic / pathology
-
Cyclophosphamide / toxicity
-
Epithelial Cells / drug effects
-
Epithelial Cells / metabolism*
-
Epithelial Cells / pathology
-
Female
-
Gene Expression
-
Genes, Reporter
-
Green Fluorescent Proteins / genetics
-
Green Fluorescent Proteins / metabolism
-
Humans
-
Keratin-14 / genetics*
-
Keratin-14 / metabolism
-
Luminescent Proteins / genetics
-
Luminescent Proteins / metabolism
-
Male
-
Mice
-
Mice, Transgenic
-
Red Fluorescent Protein
-
Regeneration / genetics*
-
Urinary Bladder / drug effects
-
Urinary Bladder / metabolism*
-
Urinary Bladder / pathology
-
Urothelium / drug effects
-
Urothelium / metabolism
-
Urothelium / pathology
Substances
-
Biomarkers, Tumor
-
Keratin-14
-
Krt14 protein, mouse
-
Luminescent Proteins
-
Green Fluorescent Proteins
-
Cyclophosphamide